Synthesis of the bis-spiroacetal moiety of the polyether antibiotic CP44,161

The syntheses of bis-spiroacetals 25a, 25c and 40 which constitute the cent ral framework of the polyether antibiotic CP44,161 4, are described. The tr icyclic bis-spiroacetal ring is formed by oxidative cyclisation of hydroxys piroacetal 9 which in turn is assembled from lactone 10 and acetylene 11. T he key stereogenic centres in acetylene 11 were assembled using a Sharpless asymmetric dihydroxylation and an Evans asymmetric alkylation of a chiral oxazolidinone. Asymmetric dihydroxylation of alkene 14 using (DHQ)(2)PHAL ( hydroquinine phthalazine-1,4-diyl diether) led to acetylene 22 which in tur n was converted to bis-spiroacetals 25a and 25c. Construction of the isomer ic acetylene 11 was effected via Sharpless asymmetric dihydroxylation of al kene 14 using the pseudoenantiomeric chiral ligand (DHQD)(2)PHAL which in t urn led to the formation of bis-spiroacetal 40 with the same configuration at C-2 as that present in antibiotic CP44,161 4. Barbier addition of bromid e 8 to bis-spiroacetal aldehyde 27 afforded alcohol 28 which was then conve rted to polyethers 32 and 33 via an epoxidation cyclization strategy. This latter reaction sequence demonstrated the feasibility of appending the E ri ng to the tricyclic bis-spiroacetal BCD ring system of antibiotic CP44,161 4.